Antitumour, Immunomodulatory activity and in silico studies of naphthopyranones targeting iNOS, a relevant target for the treatment of Helicobacter pylori infection.

The naphthopyranones paepalantine and 5-methoxy-3,4-dehydroxanthomegnin isolated from Paepalanthus sp, showed in previous studies antioxidant, anti-inflammatory, antitumour and antimicrobial potential, such as anti-Helicobacter pylori activity. H. pylori infection is one of the main causes of gastric cancer, causing an excessive inflammatory response through the neutrophils and macrophages infiltration, increasing the release of reactive species and thus inducing the production of pro-inflammatory mediators. In the present study, immunomodulatory activity of naphthopyranones in LPS-stimulated macrophages and cytotoxic action in gastric adenocarcinoma cell lines was evaluated. The potential of interaction of these substances in the iNOS binding site was investigated by molecular docking. Cytotoxic activity in gastric adenocarcinoma cells (AGS) was evaluated by the MTT assay. The results evidenced immunomodulatory potential by inhibiting the pro-inflammatory cytokines and nitric oxide produced by LPS-stimulated macrophages. Cytotoxic activity in AGS cell line was also reported. The results indicated that the studied naphthopyranones are viable alternatives in the treatment and prevention of H. pylori infection as well as the diseases related to this infection, especially gastric cancer.

Anti-Helicobacter pylori Activity of Isocoumarin Paepalantine: Morphological and Molecular Docking Analysis.

The Helicobacterpylori bacterium is one of the main causes of chronic gastritis, peptic ulcers, and even gastric cancer. It affects an average of half of the world population. Its difficult eradication depends upon multi-drug therapy. Since its classification as a group 1 carcinogenic by International Agency for Research on Cancer (IARC), the importance of H. pylori eradication has obtained a novel meaning. There is considerable interest in alternative therapies for the eradication of H. pylori using compounds from a wide range of natural products. In the present study, we investigated the antibacterial property of the isocoumarin paepalantine against H. pylori and it exhibited significant anti-H. pylori activity at a minimum inhibitory concentration (MIC) of 128 µg/mL and at a minimum bactericidal concentration (MBC) of 256 µg/mL. The scanning electron microscopy (SEM) revealed significant morphological changes of the bacterial cell as a response to a sub-MIC of paepalantine, suggesting a penicillin-binding protein (PBP) inhibition. Computational studies were carried out in order to study binding modes for paepalantine in PBP binding sites, exploring the active and allosteric sites. The data from the present study indicates that paepalantine exhibits significant anti-H. pylori activity, most likely by inhibiting membrane protein synthesis.

Preformulation study and influence of DMSO and propylene glycol on the antioxidant action of isocoumarin paepalantine isolated from Paepalanthus bromelioides

AbstractCoumarins are phenolic compounds and have various biological properties, including antioxidant activity. The isocoumarin paepalantine, isolated from of Paepalanthus bromelioides Silveira, Eriocaulaceae, exhibits a wide range of biological activities, including antimicrobial, anti-inflammatory, antioxidant and cytotoxic properties. Studies on paepalantine often use dimethylsulfoxide as a solvent. However the dimethylsulfoxide interferes with antimicrobial, cytotoxic and antioxidant assays. Thus, this study aims to evaluate alternative solvents for paepalantine and evaluate their potential to interfere with antioxidant assays (ABTS•+, O2•-, HOCl). Of the selected solvents, propylene glycol had good solubility and remained stable throughout the study period. The results suggested that there is no interference from propylene glycol in antioxidant assays, while dimethylsulfoxide significantly interfered with the HOCl assay. The antioxidant assays showed that paepalantine demonstrated similar or even better antioxidant activity than Trolox. Thus, propylene glycol may be the solvent of choice for paepalantine, a compound that has significant biological potential.